Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi

Cornick, J. E., Harris, S. R., Parry, C. M., Moore, Michael J., Jassi, C., Kamng'ona, A., Kulohoma, B., Heyderman, Robert, Bentley, S. D. and Everett, D. B. (2014) 'Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi'. Journal of Antimicrobial Chemotherapy, Vol 69, Issue 2, pp. 368-374.

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Abstract

Objectives

This study aimed to define the molecular basis of co-trimoxazole resistance in Malawian pneumococci under the dual selective pressure of widespread co-trimoxazole and sulfadoxine/pyrimethamine use.

Methods

We measured the trimethoprim and sulfamethoxazole MICs and analysed folA and folP nucleotide and translated amino acid sequences for 143 pneumococci isolated from carriage and invasive disease in Malawi (2002–08).

Results

Pneumococci were highly resistant to both trimethoprim and sulfamethoxazole (96%, 137/143). Sulfamethoxazole-resistant isolates showed a 3 or 6 bp insertion in the sulphonamide-binding site of folP. The trimethoprim-resistant isolates fell into three genotypic groups based on dihydrofolate reductase (encoded by folA) mutations: Ile-100-Leu (10%), the Ile-100-Leu substitution together with a residue 92 substitution (56%) and those with a novel uncharacterized resistance genotype (34%). The nucleotide sequence divergence and dN/dS of folA and folP remained stable from 2004 onwards.

Conclusions

S. pneumoniae exhibit almost universal co-trimoxazole resistance in vitro and in silico that we believe is driven by extensive co-trimoxazole and sulfadoxine/pyrimethamine use. More than one-third of pneumococci employ a novel mechanism of co-trimoxazole resistance. Resistance has now reached a point of stabilizing evolution. The use of co-trimoxazole to prevent pneumococcal infection in HIV/AIDS patients in sub-Saharan Africa should be re-evaluated.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 460 Genomics. Proteomics QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified. WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 210 Streptococcal infections (General or not elsewhere classified) WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1093/jac/dkt384
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	01 May 2015 11:38
Last Modified:	06 Feb 2018 13:09
URI:	https://archive.lstmed.ac.uk/id/eprint/5119

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